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Synthesis and 3 D ‐ QSAR Analysis of 2‐Chloroquinoline Derivatives as H 37 RV MTB Inhibitors
Author(s) -
Khunt Ranjan C.,
Khedkar Vijay M.,
Coutinho Evans C.
Publication year - 2013
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12178
Subject(s) - antimycobacterial , quantitative structure–activity relationship , stereochemistry , chemistry , in vitro , combinatorial chemistry , mycobacterium tuberculosis , computational biology , tuberculosis , computer science , biology , biochemistry , medicine , pathology
Frequency of tuberculosis is progressively increasing worldwide. New emerging strains of bacilli that are emerging are resistant to the currently available drugs which make this issue more alarming. In this regard, a series of substituted quinolinyl chalcones, quinolinyl pyrimidines, and pyridines were synthesized and evaluated for their antitubercular activity in vitro against M ycobacterium tuberculosis H 37 RV . To establish the role of the 2‐chloroquinoline nucleus as a pharmacophoric group and study its influence on the antimycobacterial activity, a 3 D ‐ QSAR study based on C o MFA and C o MSIA was undertaken on this set of 2‐chloroquinoline derivatives. Statistically significant models that are able to well correlate the antimycobacterial activity with the chemical structures of the 2‐chloroquinolines have been developed. The contour maps resulting from the best C o MFA and C o MSIA models were used to identify the structural features relevant to the biological activity in this series of analogs. Further analysis of these interaction‐field contour maps also showed a high level of internal consistency. The information obtained from the field 3‐ D contour maps may be fruitfully utilized in the design of more potent 2‐chloroquinoline‐based analogs as potential antitubercular candidates.